Kaposi's Sarcoma-Associated Herpesvirus-Encoded Viral IL-6 (vIL-6) Enhances Immunoglobulin Class-Switch Recombination

Kaposi's Sarcoma-Associated Herpesvirus-Encoded Viral IL-6 (vIL-6) Enhances Immunoglobulin Class-Switch Recombination

Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic gamma-herpesvirus that causes AIDS-associated Kaposi sarcoma (KS) and several lymphoproliferative disorders. During the humoral immune response antigen-activated mature B cells acquire functional diversification by immunoglobulin he...

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Bibliographic Details
Published in:Frontiers in microbiology Vol. 9; p. 3119
Main Authors: Rosario, Santas A, Santiago, Gabriel E, Mesri, Enrique A, Verdun, Ramiro E
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 18-12-2018
Subjects:
adaptive immunity
class-switch recombination
heavy chain constant region
Kaposi’s sarcoma-associated herpesvirus
Microbiology
microhomology
viral IL-6
Kaposi’s sarcoma-associated herpesvirus
activation-induced cytidine deaminase
microhomology
heavy chain constant region
viral IL-6
adaptive immunity
class-switch recombination
classical non-homologous end joining
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Summary:Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic gamma-herpesvirus that causes AIDS-associated Kaposi sarcoma (KS) and several lymphoproliferative disorders. During the humoral immune response antigen-activated mature B cells acquire functional diversification by immunoglobulin heavy chain (IgH) class-switch recombination (CSR). CSR is initiated by activation-induced cytidine deaminase (AID) which targets highly repetitive switch (S)-regions to mediate DNA double-stranded breaks (DSBs) in the IgH locus facilitating intramolecular recombination. Here we show that in the context of cytokine stimulation, CSR is enhanced in murine B cells exposed only to replication-competent KSHV in an environment of KSHV infection, which coincided with elevated AID transcripts. Using murine splenic B cells and the mouse lymphoma CH12F3-2 CSR system, we identified that vIL-6, but not murine IL-6, increased class-switching, which correlated with upregulated AID expression. Together, these data suggest a regulatory role for KSHV vIL-6 in functionally modulating B cell biology by promoting CSR, which may in part explain how KSHV infection influences humoral immunity and affect KSHV pathogenesis.
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This article was submitted to Virology, a section of the journal Frontiers in Microbiology
Reviewed by: Keiji Ueda, Osaka University, Japan; Satoshi Ishido, Hyogo College of Medicine, Japan
Edited by: Akio Adachi, Kansai Medical University, Japan
ISSN:1664-302X
1664-302X
DOI:10.3389/fmicb.2018.03119